Journal article
Epithelial sel1L is required for the maintenance of intestinal homeostasis
S Sun, R Lourie, SB Cohen, Y Ji, JK Goodrich, AC Poole, RE Ley, EY Denkers, MA Mcguckin, Q Long, GE Duhamel, KW Simpson, L Qi
Molecular Biology of the Cell | AMER SOC CELL BIOLOGY | Published : 2016
Abstract
Inflammatory bowel disease (IBD) is an incurable chronic idiopathic disease that drastically decreases quality of life. Endoplasmic reticulum (ER)-associated degradation (ERAD) is responsible for the clearance of misfolded proteins; however, its role in disease pathogenesis remains largely unexplored. Here we show that the expression of SEL1L and HRD1, the most conserved branch of mammalian ERAD, is significantly reduced in ileal Crohn's disease (CD). Consistent with this observation, laboratory mice with enterocyte-specific Sel1L deficiency (Sel1LδIEC) develop spontaneous enteritis and have increased susceptibility to Toxoplasma gondii- induced ileitis. This is associated with profound defe..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
We thank Lora Hooper (UT Southwestern, Dallas, TX) for generous gifts of antibodies and other members of the Qi lab for comments, suggestions, and technical assistance. This work was supported by National Institutes of Health Grants R21AI085332 (G.D.) and R21AI09061 (E.Y.K.), Chinese National Natural Science Foundation Grant 31371391 (to Q.L.), National Institutes of Health Grants 1R01GM113188 and 1R01DK105393, Juvenile Diabetes Research Foundation Grant 47-2012-767, and American Diabetes Association Grant 1-12-CD-04 (L.Q.). S.S. is an International Student Research Fellow of the Howard Hughes Medical Institute (59107338). R.L. is the recipient of a Betty McGrath Mater Practitioner Research Fellowship. L.Q. is the recipient of Junior Faculty and Career Development Awards from the American Diabetes Association.